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A Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) (NSC 330507) Via Intravenous Administration in Patients With Advanced Malignancies


Phase 1
18 Years
75 Years
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) (NSC 330507) Via Intravenous Administration in Patients With Advanced Malignancies


OBJECTIVES:

- Determine the maximum tolerated dose for a geldanamycin analogue,
17-allylamino-17-demethoxygeldanamycin (AAG), in patients with advanced malignancies.

- Determine the toxic effects and dose-limiting toxicity of AAG in this patient
population.

- Determine the safe dose of AAG for a Phase II study.

- Measure the pharmacokinetic and pharmacodynamic profiles of AAG in these patients.

- Assess time to tumor progression and any antitumor activity in patients treated with
AAG.

OUTLINE: This is a dose-escalation study.

Patients receive a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), IV
over 15-30 minutes every week. Treatment continues in the absence of disease progression or
unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AAG until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6
patients experience dose-limiting toxicity.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically proven malignancies refractory to conventional
treatment or for which no standard therapy exists

- Primary brain tumor or brain metastases allowed if stable symptoms within 2 weeks
prior to study and able to give informed consent

PATIENT CHARACTERISTICS:

Age:

- 18 to 75

Performance status:

- WHO 0-2

Life expectancy:

- At least 3 months

Hematopoietic:

- WBC at least 3,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 10.0 g/dL

- Absolute neutrophil count at least 1,500/mm^3

Hepatic:

- Bilirubin less than 1.0 mg/dL

- AST and ALT no greater than 2.5 times upper limit of normal if due to liver
metastases

- No chronic liver disease

Renal:

- Creatinine less than 1.47 mg/dL OR

- Creatinine clearance greater than 60 mL/min

Cardiovascular:

- No myocardial infarction within the past 6 months

- No angina requiring treatment within the past 6 months

- No uncompensated coronary artery disease by electrocardiogram or physical examination

- No prior transient ischemic attacks, stroke, or peripheral vascular disease

- LVEF at least 45%

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 weeks after study

- No allergy to egg products

- No nonmalignant systemic disease that would increase risk

- No active uncontrolled infection

- No diabetes mellitus with evidence of severe peripheral vascular disease or diabetic
ulcers

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
and recovered

- No other concurrent chemotherapy

Endocrine therapy:

- At least 4 weeks since other prior endocrine therapy and recovered

- Concurrent corticosteroids for symptom control allowed if no change in dose
requirement within 2 weeks prior to study

Radiotherapy:

- At least 4 weeks since prior radiotherapy (except for palliative reasons) and
recovered

- Concurrent radiotherapy allowed for control of bone pain or as indicated

Surgery:

- Not specified

Other:

- No other concurrent investigational treatment

- No concurrent treatment with drugs interfering with hepatic CYP3A4 metabolism (e.g.,
grapefruit juice or warfarin)

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Recommended phase II dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) at 4 weeks

Safety Issue:

Yes

Principal Investigator

Ian R. Judson, MA, MD, FRCP

Investigator Role:

Study Chair

Investigator Affiliation:

Royal Marsden NHS Foundation Trust

Authority:

United States: Federal Government

Study ID:

CRC-PHASE-I-PH1/074

NCT ID:

NCT00003969

Start Date:

August 1998

Completion Date:

January 2007

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific

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